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Indian Journal of Environmental Sciences 21(1), 2017, pp. 1-34 ISSN 0971-8958
Green Earth Foundation
CRITICAL ANALYSIS OF PROTECTIVE ROLE OF PLANTS AGAINST
GENTAMICIN INDUCED NEPHROTOXICITY
Nirmala Yadav, Shweta Sharma1*, Subhasini Sharma1 and K.P. Sharma
Botany Department, University of Rajasthan, Jaipur -302004
1Zoology Department, University of Rajasthan, Jaipur -302004
*Author for correspondence
Abstract
Nephrotoxicity is one of the most common kidney problems caused by variety of toxic compounds.
Gentamicin (GM) is a broad spectrum aminoglycoside commonly used for controlling life threatening
infections caused by Gram (+ve) and Gram (-ve) bacilli. However, it causes nephrotoxicity in about 15-
30% of treated subjects. Because of superiority of gentamicin in controlling life threatening infections,
scientific community is exploring renoprotective role of plant species to minimize gentamicin induced
nephrotoxicity. In the present review, we have critically evaluated studies made for exploring renoprotective
role of 2 species of algae, 3 of fungi, 1 of gymnosperm and 145 of angiosperms in the experimental animals
exposed to gentamicin (GM). Histopathological findings of kidney are not considered in this review since
these are merely descriptive (qualitative) and therefore, comparison among plant species is difficult for
identifying the most promising renoprotective plant species. Ameliorating role of plant species has been
considered in view of protection/recovery in the serum biochemical parameters deciphering kidney functions
(urea, creatinine, uric acid, blood urea nitrogen) and oxidative stress (MDA/LPO, GSH/GPX, CAT,
SOD). Out of 151species screened in the gentamicin treated animals, majority (108 species) were
renoprotective (moderate – excellent) and reduce oxidative stress. It is likely that they differ in biomolecules.
Plant species of excellent category may therefore, be explored for their ameliorative role to other
nephrotoxicants both singly as well as in various combinations. The recommended dose of gentamicin for
human is 20µg/kg body weight while several plant species were excellent in term of protection to experimental
animals even at its higher doses (80-100mg/kg body weight), and therefore, there is a good scope for their
clinical trials in the human beings treated with gentamicin. Presence of renoprotective properties among
such a vast number of species highlights role of biodiversity in the welfare of mankind.
Key Words: Antioxidant, Creatinine, Gentamicin, Nephrotoxicant, Renoprotective plant species, Urea
Kidney is the only organ in the body that removes metabolic
wastes such as urea, creatinine, uric acid etc. from the blood
which are excreted through urine. Beside metabolic wastes;
kidney also removes drugs and various toxic industrial and
environmental agents in the blood. Because of increased
blood flow (25% of the cardiac output) and presence of
cellular transport systems within epithelial cells of the nephron,
exposure to toxic substances is maximum in kidney. As a
result, kidney related diseases are on rise particularly in the
relatively more polluted areas.
Nephrotoxicity is one of the most common kidney problems
with an estimated lifetime risk of 2-5% in Asia, 8-15% in
Europe, America and around 20% in the Middle East. It
reduces glomerular filtration rate that raises level of blood
urea nitrogen (azotemia) and creatinine in the serum leading
to increased retention of fluids in the body (over hydration)
and blood pressure (hypertension).
The ability of kidney to concentrate tubular fluid contents is a
hallmark of renal function. The nephrotoxic compounds
damage epithelial cells of tubules; thereby reduce urine
concentrating capacity or tubular proteinuria, lysosomal
enzymuria and mild glucosuria, decrease ammonium excretion
and increase hydrogen ion concentration in the blood
(acidosis). The outcome is concentration gradient which favors
Yadav et al.2
influx of toxic compounds from the tubular fluid to the blood.
This causes severe complications in the body such as edema,
ascites, hepatomegaly etc. leading to acute renal failure.
The toxic compounds may be exogenous or endogenous.
Radio contrast agents, aminoglycosides, antibiotics,
chemotherapeutic agents, organic solvents, acetaminophen,
illegal abortifacients, antineoplastic agents like
cyclophosphamide, vincristin, cisplatin etc are important
exogenous toxic agents. Their prolonged exposure may cause
irreversible damage to renal system resulting in chronic renal
failure (CRF), which led to permanent loss of excretory and
endocrine functions of kidney.
Nephrotoxicants
Several toxicants may cause kidney failure. Following are
some of the important nephrotoxic agents.
A) Metals & metalloid: Aluminum and its compound
such as aluminum fluoride, Heavy metals such as
mercury, cadmium, chromium, tin, lead, etc., and
metalloid - arsenic
B) Antineoplastic agents
· Alkylating agents: Cisplatin, cyclophosphamide
· Nitrosoureas: Streptozotocin, carmustine,
lomustine & semustine
· Antimetabolites: High doses of methotrexate,
cytosine arabinose, 6-thioguanine, 5-flurouracil
· Antitumor antibiotics: Mitomycin, mithramycin,
doxorubicin
· Biologic agents: Recombinant leukocyte and
interferon
C) Antimicrobial agents: Tetracycline, acyclovir,
pentamidine, sulphadiazine, trimethoprin, rifampicin,
amphotericin-B
D) Aminoglycosides: Gentamicin, amikacin, kanamycin,
streptomycin
E) Anti-cancer drugs
· Cyclosporine
· Cisplatin
· Cyclophosphamide
· Methanoglobin forming agents
F) Miscellaneous
· Radiocontrast agents: Non-steroidal anti-
inflammatory agents (NSAID’s), ibuprofen,
indomethacin, aspirin etc.
· Liquor consumption
G) Solvents and fuels
· Carbon tetrachloride
· Methanol
· Amyl alcohol
· Glycol
G) Environmental agents
· Fluoride
· Acid rains
I) Others
· Herbicides
· Pesticides
· Diseases stimulating overproduction of uric acid
Mechanism of Nephropathy
Nephrotoxic agents damage tubular epithelial cells either by
reacting directly with cellular macromolecules and membrane
components or indirectly through their metabolism. Heavy
metals (Hg, Pb), organic cations (spermine, cationic amino
acids, amino glycosides) and polyene antibiotics
(amphotericin) interacting respectively with sulfhydryl groups,
membrane phospholipids and cholesterol cause direct
damage whereas indirect damage is caused by metabolites
(fluoride and oxalates) formed in hepatic metabolism of
methoxyflurane intermediates of cisplastin, cystine conjugates,
cephaloridine and acetaminophen. These toxic metabolites
also generate free radicals.
Neprotoxicant accumulate mainly in the proximal
tubular epithelial cells
Proximal straight (PT) and distal convoluted tubules (DT) of
kidney are the major targets of toxicants since these
accumulate in their epithelial cells. Because of brush border
epithelial cells, PT absorbs and metabolizes toxicant more
efficiently. This reduces exposure of DT cells to toxicant.
Alterations in the DT cells are therefore, relatively less than
that of proximal tubule cells (PT). The excessive injury in
tubules lead to necrosis of tubular epithelial cells that
significant increase urinary excretion of both brush border
(alkaline phosphatase, g-glutamyl transferase) and
intracellular enzymes (LDH, aspartate aminotransferase,
alanine aminotransferase, and N-acetyl-b-D-
glucosaminidase) (Agency for Toxic Substance and Disease
Registry 1994, Gotelli et al. 1985, Guyton and Hall 2006,
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 3
Planas-Bohne 1977, Price 1982, World Health Organization
1991, Zalups and Diamond 1987, Zalups et al. 1988, Zalups
1998).
Neprotoxicants also alter activity of many enzymes like acetyl
cholinesterase, hexokinase, phosphor-oxidase and adenyl
cyclase, aspartate aminotransferase (AST), alanine amino
transferase (ALT), acid and alkaline phosphatase and
phophorylase, lactate dehydrogenase (LDH), NADP (H)
oxidase, lipases and phospholipases, creatinine
phosphokinase etc.
Various studies have pointed out that nephrotoxicants
increase oxidative stress either through excessive production
of reactive oxygen species (ROS) such as superoxide radical
(O2
-), H2O
2 and hydroxyl radical (OH-) or disturb redox
balance in the body by decreasing the activity of endogenous
free radical scavengers such as superoxide dismutase,
glutathione peroxidase and catalase. This leads to destruction
of intracellular organelles, loss of microvilli, alterations in the
number and size of the lysosomes and mitochondrial
vacuolization followed by functional alterations such as DNA
damage, inhibition of protein synthesis, glutathione depletion,
lipid peroxidation and apoptosis. Because of excessive
accumulation of free radicals, kidney loss copper and zinc
that favor peroxidation of lipids and depletion of glutathione
(Srinivasan et al. 2011, Ahmed and Sajida 2012, Ammar
and Sabah 2013).
Na+-K+ ATPase and Ca+2-Mg+2ATPase pumps regulate
urinary Na+ and Ca+2 losses from serum. Neprotoxicant
decreases activity of Na+-K+ ATPase and Ca+2-Mg+2ATPase
pumps (Cittanova 2002, Anner and Moosmayer 1982,
Anner et al. 1983, Imesch et al. 1992) and also alter
membrane permeability. This may allow increased fluid
uptake and its accumulation in cell vacuoles. Neprotoxicant
also reduces reabsorption of number of plasma solutes such
as glucose, amino acids, albumin, and other plasma proteins
(Price 1982, Zalups and Diamond 1987, Zalups et al. 1998).
The binding of different nephotoxicants with aquaporins
blockade their function. Neprotoxicants render the collecting
duct unresponsive to vasopressin or decrease vasopressin
induced CAMP generation that leads to polyuria, polydipsia
and weight loss (Turner et al. 1989, Yadav et al. 2016).
Nephrotoxicant inhibits protein synthesis in the renal cells
that induces necrosis of cells in the proximal tubule which
can lead to acute renal failure (Sundin et al. 2001).
Gentamicin (GM) is a broad spectrum aminoglycoside
commonly used for controlling life threatening infections
caused by Gram (+ve) and Gram (-ve) bacilli. The epithelial
cell linings of certain segments of the proximal renal tubules
retain almost 5% of administered dose of gentamicin causing
nephrotoxicity in about 15-30% of treated subjects evinced
by increase in levels of creatinine, urea, uric acid/ blood urea
nitrogen in the serum. Gentamicin also acts as an iron chelator
and the iron-gentamicin complex is a potent catalyst of free
radical generation resuting in oxidative stress. Because of
superiority of gentamicin in controlling life threatening
infections, scientific community is exploring ways to minimize
gentamicin induced nephrotoxicity.
Medicinal Plants possessing nephroprotective activity
Therapeutic use of plants popular in underdeveloped and
developing countries is now gaining acceptance worldwide
because of its minimum/ almost nil side effects. Ayurveda is
the medical science flourished in India in which ailments are
cured with locally available medicinal plants. Because of
diverse climate, India is a treasure of medicinal plants.
Medicinal properties of plants are due to alkaloids,
terpenoids, steroids, essentials oils and antioxidants such as
vitamins, flavanoids, phenols etc. As stated earlier,
neprotoxicants induces renal toxicity by increasing ROS
generation and lipid peroxidation and therefore, medicinal
plants rich in antioxidants may find application in minimizing
neprotoxicant toxicity. Phytochemicals may also reduce levels
of creatinine, urea, uric acid/ blood urea nitrogen in the serum
and thereby improve GFR.
Scientists have explored nephroprotective role of plant
species used since ages either by the locals or reported in
Materia Medica of the ancient system of medication, other
than conventional allopathic system of medication. In the
present review, we have critically evaluated studies made
for exploring renoprotective role of 2 species of algae, 3 of
fungi, 1 of gymnosperm and 143 of angiosperms in the
experimental animals exposed to gentamicin (GM).
Based on delivery of plant extract/powder (herbal
preparation) to the experimental animals during the study,
following 3 types of treatments were identified.
1. Concomitant- GM and herbal preparation were
administered simultaneously. Herbal preparation
given prior to GM exposure on the same day was
also considered concomitant.
Yadav et al.4
2. Preventive- Herbal preparation was administered
to the experimental animals prior to entry into
experimental protocol.
3. Curative- Herbal preparation was administered
following GM exposure.
Histopathological findings of kidney are not considered in
this review since these are merely descriptive (qualitative)
and therefore, comparison among plant species is difficult
for identifying the most promising renoprotective plant
species. Ameliorating role of plant species has been
considered in view of protection/recovery in the serum
biochemical parameters deciphering kidney functions (urea,
creatinine, uric acid, blood urea nitrogen) and oxidative stress
(MDA/LPO, GSH/GPX, CAT, SOD). Further, protection
level is classified in to following 6 grades.
A: Values of aforesaid parameters were almost similar to
control {values of kidney markers and oxidative stress were
higher (1-20%) than control values while of antioxidant levels
were lower (1-20%)} than control.
B: Values of aforesaid parameters were more (21-30%)
than control values for kidney markers and oxidative stress
but lesser (21-30%) for antioxidant levels.
C: Values of aforesaid parameters were more (31-50%)
than control values for kidney markers and oxidative stress
but lesser (31-50%) for antioxidant levels.
D: Values of aforesaid parameters were more (51-70%)
than control values for kidney markers and oxidative stress
but lesser (51-70%) for antioxidant levels.
E: Values of aforesaid parameters were more (>70%) than
control values for kidney markers and oxidative stress but
lesser (>70%) for antioxidant levels.
Symbol AA has been assigned to denote recovery in
parameter/s even better than control; say for example when
urea, creatinine and MDA/LPO levels were even lesser than
control values and vice versa for antioxidants. The critical
analysis of available data has been tabulated (Table 1-5).
Based on quantum of serum biochemical data reported in
various studies, data have been tabulated as follows.
1. Data on kidney functions + antioxidants levels at the
termination of study
2. Data on kidney functions + antioxidants levels at
different time intervals during the study period
3. Data on kidney functions at the termination of study
4. Data on kidney functions at different time intervals
during the study period
Comparing values of serum biochemical parameters (denoting
kidney functions, oxidative stress and antioxidant levels) in
the gentamycin treated animals vis a vis control, following
three categories were assigned to decipher ameliorating role
of plant species.
1. Excellent (E): This includes plant species showing
recovery of parameters in to ‘AA ‘and ‘A’ grades.
2. Good (G): This includes plant species showing
recovery of all parameters into ‘A’ grades.
3. Moderate (M): This includes plant species showing
recovery of few parameters into either ‘AA ‘or ‘A’ grade
whereas of others in the lower grades. In case of only
kidney parameters, one parameter may be of lower
grade whereas for both kidney and oxidative stress
parameters, two parameters may be of lower grade.
4. Poor (P): This includes plant species showing recovery
of one parameter each of kidney function and oxidative
stress into either ‘AA ‘or ‘A’ grade whereas of others
in the lower grades.
In majority of studies, optimum protection to the animals
was accorded when gentamicin and herbal formulation were
administered concomitantly. Normally renoprotection action
of herbal formulation was dose dependent but an opposite
trend was observed in few species.
· The protection/recovery of kidney functions and
oxidative stress was moderate when algae and fungi
were administered to the gentamicin treated animals
(Table 1).
· The protection/recovery of kidney functions belonged
to excellent category when plant parts of following
plant species were administered to the gentamicin
treated animals (Table 2-5).
Belowground organs
Root: Croton zambesicus, Hemidesmus, Panax, Ipomea
digitata
Bulb: Allium sativum
Tuber: Myrmecodia
Aboveground organs
Leaf: Casurina, Euclea, Psidium, Kalanchoe, Mentha
and Moringa
Shoot: Eryngium
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 5
Table 1. Ameliorative role of algae, fungi and gymnosperm on biochemical markers of kidney health and oxidative stress.
U = Urea, C = Creatinine, BUN = Blood urea nitrogen, UA = Uric acid, NA = Not available, Etha. = Ethanol, Ext.= Extract, d = day
Bark: Spathodea and Cinnamomum zylenicum
Gum: Acacia senegal
Fruit: Solanum nigram, Citrus aurantium, Mangifera
Seed: Benincosa, Carica, Foenculum, Nigella,
Trachyspermum
Whole plant: Hygrophila, Cuscuta, Kigelia, Morinda and
Terminalia chebula
Seeds of Foeniculum in combination with fruits of Solanum
nigrum also protected kidney function under excellent
category.
· The plant parts of following plant species protected/
recovered kidney functions to good category (Table
2-5).
Belowground organs
Root: Cassia auriculata, Cyperus, Glycirrhiyza, Garcina
kola
Rhizome: Zinziber
Aboveground organs
Leaf: Aloe, Aegle mermelos, Apium, Callestimon,
Cynara, Urtica, Bryophyllum, Ficus carica, Sesbania
grandiflora
Shoot: Phyllanthus flaternus
Bark: Ficus racemosa
Flower: Calotropis, Cocos nucifera, Crocus sativus,
Punica
GM
(mg/
Kg B. wt)
Plant Herbal
Prep- Dose Protocol
ration mg/kg
B. wt
Prognosis References
Kidney functions Oxidative stress
U C BUN/UA*
LPO/ MDA*
GSH/ GPX*
CAT SOD
100 (1-7d)
Spirulina platensis
Whole plant
1000 Concomitant (1-7d)
D A D* B/A
* A Karadeniz
et al.
2008a 80
(3-10d)
Spirulina
fusiformis
Whole
plant
500 Preventive
(1-2d) + Concomitant
(3-10d)
E E
D C Kuhad et
al. 2006
1000 E E C B
1500 A C A A
50
(1-6d)
Morchella
esculenta
Mycelia:
Hydro- ethan. Ext.
250 Concomitant
(1-6d)
E E A* A/B* B B Nitha and
Janardhanan 2008
500
C E C* C/A* A A
100
(1-8d)
Pleurotus
porrigens
Meth. Ext.
(dried fruiting
body)
200 Concomitant
(1-8d) + Curative
(9-10d)
D D A Moghadda
m et al. 2010
400 C B AA
100
(1-7d)
Sacchar-
omyces cerevisiae
Whole
plant
50%
of diet
Curative
(6-56d)
AA C A*
C C B EL-Ghany
et al. 2012
80 (1-7d)
Volvariella volvacea
Fruiting body:
Aqua Ext.
500 Concomitant (1-7d)
A D E*
A/C* A B Kalava
and
Menon 2012
1000 A A B* A/A* A A
80 (3-10d)
Ginkgo biloba
Leaf Ext.
(Ranbaxy lab.)
300 Preventive (1-2d) +
Concomitant (3-10d)
AA
D B*
Naidu et al. 2000
100
(1-8d)
Leaf :
Etha. Ext.
200 Concomitant
(1-8d)
E E D/C* Mansoor
et al. 2015 400 B B C/A*
Yadav et al.6
Table 2. Ameliorative role of plant species on biochemical markers of kidney health.
GM
(mg/ kg
B. wt)
Plant Herbal
Prep. Dose Protocol
mg/kg
B. wt
Prognosis : Kidney
functions
References
U C BUN/
UA*
100
(1-7d)
Abutilon indicum Root:
Etha.
Ext.
150 Concomitant
(1-7d)
E A Jesurun and
Lavakumar 2016 300 D A
100
(1-8d)
Acacia senegal Gum
arabic:
Aqua.
Ext.
670 Concomitant
(1-8)
AA
A Tahir et al. 2016
80
(5-10d)
200 Preventive
(1-4d) +
Concomitant
(5-10d)
E E Ali et al. 2003
80
(1-8d)
Adhatoda
zeylanica
Leaf:
Etha.
Ext.
500 Curative
(9 d -18d)
E AA Kumar et al. 2013
40
(1-13d)
Aerva lanata
Whole
plant:
Etha.
Ext.
75 Curative
(14-23d)
E E Shirwaikar et al. 2004
150 C E
300 A E
300 Concomitant
(1-13d)
D E
100
(3- 9d)
Althaea officinalis Flower:
Etha.
Ext.
50 Preventive
(1-2d) +
Concomitant
(3-9th d)
E E Talebi et al. 2014
250 E E
500 E E
100
(1-14d)
Allium cepa Leaf:
Etha.
Ext.
200 Concomitant
(1-14d)
E Chinnala et al. 2017
400 E
120
(1-14d)
Allium sativum Cloves:
Aqua
Ext.
4% of
diet
Concomitant
(1-14d)
AA A Seckiner et al. 2014
10
(1-10d)
Cloves:
Etha.
Ext.
20
Concomitant
(1-10d)
A A Nasri et al. 2013
Curative
(11-20d)
C D
80
(1-7d)
Aloe barbadensis
Leaf:
Aqua
Ext.
100 Concomitant
(1-7d)
E E A* Chatterjee et al. 2012
200 C E AA*
80
(1-8d)
Andrographis
paniculata
Root:
Aqua
Ext.
200 Concomitant
(1-8d) +
Curative
(9-10d)
A A C Singh et al. 2009
100
(1-8d)
Bauhinia
purpurea
Leaf:
Etha.
Ext.
300
Concomitant
(1-8d)
D E D/B* Laxmi et al. 2009
Unripe
Pod:
Etha. Ext.
B B A/A*
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 7
100
(1-8d)
Bauhinia
variegata
Fruit:
Aqua
Ext.
200
Concomitant
(1-8d)
E E E Sharma et al. 2011
Fruit:
Etha.
C E E
Fruit:
Aqua
400 E E E
Fruit:Etha. A C C
Leaf :
Meth. Ext
400 Concomitant
(1-8d)
A B A/A* Prusty et al. 2012
80
(1-6d)
Benincosa hispida Seed :
Etha.
Ext.
250 Concomitant
(1-6d)
AA E Qadrie et al. 2013
500 AA A
80
(1-10d)
Boerhavia diffusa
Himalaya
capsule
Plant Ext.
400 Curative
(11-74d)
E E E* Padmini and Kumar
2013 800
C C C*
80
(1-8d)
Root 4g/kg Concomitant
(1-8d) +
Curative
(9-21d)
A E Kulkarni et al. 2012
Curative
(9-21d)
A A
100
(1-8d)
Boswellia serrata Gum: Aqua
extract
1000 Concomitant
(1-8d)
D E Alam et al. 2011
Metha.
solub.
(MS)
650
(MS)
C E
Insolu.
(MINS)
350
(MINS)
C E
80
(1-16d)
Bryophyllum
pinnatum
Leaf:Etha.
Ext.
150 Concomitant
(1-16d)
A A Sule and Arhoghro
2016a 300 A A
40
(1-14d)
Carica papaya Seed:Aqua
Ext.
200 Concomitant
(1-14d)
AA A/A
* Nale et al. 2012
40
(1-13d)
Cassia auriculata
Root:
Etha. Ext.
600 Concomitant
(1-13d)
A A
Annie et al. 2005
600 Curative
(14-23d)
A A
100
(1-8d)
Camellia sinensis Leaf:Etha.
Ext.
300 Preventive
(1-7d) +
Concomitant
(8-15d)
C E Veljković et al. 2015
80
(1-7d)
Caesalpinia
bonduc
Leaf:Metha
Ext.
250 Concomitant
(1-7d)
E
Noorani et al. 2011
500 D
100
(1-8d)
Callestimon
viminalils
Leaf: Hydro-
metha. Ext.
250
500
Concomitant
(1-8d)
A A A/A* Sallem et al. 2016
Yadav et al.8
80
(1-21d)
Cinnamomum
tamala
Leaf:
Etha.
Ext.
200 Concomitant
(1-21d)
D A/A* Ullah et al. 2013a
100
(1-28d)
Cinnamomum
zeylanicum
Peel
powder:
Etha.
Ext.
50 Concomitant
(1-28d)
B E/D* Tanomand and Naja fian 2013
100 AA
E/A*
200 AA A/A*
80
(1-21d)
Citrullus
colocynthis
Whole
plant:
Etha.
Ext.
25 Concomitant
(1-21d)
E E/D* Ullah et al. 2013b
80
(1-7)
Cola nitida Fruit:
Aqua
Ext.
200 Concomitant
(1-7d)
E E
Abou et al. 2016
500 E D
Fruit:
Etha.
Ext.
200 E E
500 E D
90
(1-7d)
Costus afer Leaf:
Aqua
Extra.
375 Concomitant
(1-7d)
AA
E
Ezejiofor et al. 2014
750 E E
1125 AA
E
100
(1-10d)
Curcuma longa
(CL)
Rhizome
: Curcu-
min
pigment
200 Concomitant
(1-10d)
C A D* Azab et al. 2014
75 + 75
at 12h
interval
400 Preventive
(1-5d)+
Concomitant
(6-12d)
E E Negrette-Guzmán et
al. 2015
In vitro study
80
(1-6d)
Crocus sativus
Safranal:
Aqua
extract
0.5mL/
kg
B.wt.
Concomitant
(1-6d)
A A Boroushak and
Sadeghnia 2009
80
(1-14d)
Petal:
Hydro
Etha.
Ext.
40 Concomitant
(1-14d)
C C/A* Omidi and Torabi
2016 80
80
E E/A*
80
(7-14d)
Preventive
(1-6d)
D D/A*
100
(1-10D)
Saffron:
Aqua
extract
5 Concomitant
(1-10d)
E E Derakhshanfar et al.
2015
40
(1-10d)
Stigma:
Etha.
Ext.
50 Concomitant
(1-10d)
A A Dhar et al. 2013
100
(1-8d)
Croton
zambesicus
Root:
Etha.
Ext.
27 Concomitant
(1-8d)
AA AA A* Okokon et al. 2011
54 AA
AA
A*
81 AA AA A*
100
(1-8d)
Cuscuta reflexa Whole
plant :
Hydro
metha.
Ext.
200 Concomitant
(1-8d)
A A C/C* Alamgeer et al. 2017
400 A AA B/C*
600 A AA A/A*
100
(1-12d)
Dalbergia sissoo Leaf :
Etha.
Ext.
100 Concomitant
(1-12d)
C C E* Saxena et al. 2016
200 B A C*
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 9
100
(1-8d)
Daucus carota Root:
Etha.
Ext.
200 Concomitant
(1-8d)
C E C/C* Sodimbaku et al.
2016 400 A C B/B*
80
(1-5d)
Echinodorus
macrophyllus
Leaf :
Etha.
Ext.
30 Concomitant
(1-5d)
C Portella et al. 2012
80
(1-7d)
Elephantopus
scaber
Leaf:
Etha.
Ext.
200 Concomitant
(1-7d)
E E
Sahoo et al. 2012
400 D E
600 A E
80
(1-8d)
Elettaria
cardmomum
Seed:
Aqua
Ext.
100 Curative
(9-21d)
C D
Elkomy et al. 2015
200 A C
80
(1-7d)
Entandrophra
gmaangolense
Bark :
Aqua
Ext.
200 Concomitant
(1-7d)
E E
Abou et al. 2016
500 E D
Bark:
Etha.
Ext.
200 E E
500 E D
100
(1-10d)
Eryngium
caucasicum
Shoot:
Hydro-
metha.
Ext.
200 Concomitant
(1-10d)
B B C Eslami et al. 2011
400 AA A AA
200
(1-8d)
Ficus carica Leaf:
Etha.
Ext.
400 Concomitant
(1-8d)
A A Ghafoor et al. 2015
80
(1-14)
Garcina kola Root:
Metha.
250 Concomitant
(1-14d)
A AA B* Komolafe et al. 2016
Dichlo.
methane
fraction
A AA
B*
80
(1-7d)
Gomphrena celosioides
Aqua.
Ext.
(Leaf +
Stem +
Flower)
200 Concomitant
(1-7d)
E E
Abou et al. 2016
500 E D
Etha.
Ext.
(Leaf +
Stem +
Flower)
200 Concomitant
(1-7d)
E E
500 E D
90
(1-6d)
Hemidesmus
indicus
Root
Powder
5000 Curative Male
(7-12d) Female
A A Kotnis et al. 2004
A AA
80
(7-14d)
Ipomoea aquatica Leaf:
Etha.
Ext.
500 Preventive
(1- 6d)
D A Sharmin et al. 2016
40
(1-14d)
Jasminum
grandiflorum
Leaf:
Meth.
Ext.
100 Concomitant
(1-14d)
E E E/E* Venkataiah et al.
2013 200 D D C/C*
Yadav et al.10
100
(4-8d)
Khaya
senegalensis
Stem
bark:
Aqua.
Ext.
250 Preventive
(1- 3d) +
Concomitant
(4-8d)
E AA El Badvi et al. 2012
500 E C
80
(1-7d)
Kigelia africana Whole
plant:
Metha.
Ext.
100 Concomitant
(1-7d)
AA A Hoque et al. 2016
200 C E
100
(1-8d)
Kalanchoe
pinnata
Leaf :
aqua
Ext.
125 Concomitant
(1-8d)
A AA A/A* Harlalka et al. 2007
80
(1-8d)
Lagenaria
siceraria
Seed:
Metha.
Ext.
250 Concomitant
(1-8d)
A B/A* Mahurkar et al. 2012
Seed:
Aqua.
Ext.
250 A A/A*
100
(1-7d)
Lantana camara Root:
Etha.
Ext.
200 Concomitant
(1-7d)
E E C Vyas and Argal 2012
40
(1-14d)
Momordica
charantia
Leaf :
Hydro-
Etha.
Ext.
100 Concomitant
(1-14d)
E E
Chawari et al. 2011
200 E D
100
(1-10d)
Morinda citrifolia Ext.
500 Concomitant
(1-10d)
AA AA Anitha and Dass
2014
100
(1-12d)
Nelumbo nucifera Root:
Etha.
Ext.
100 Concomitant
(1-12d)
A A B* Dubey et al. 2014
Flower:
Etha.
Ext.
100 B B E*
Leaf :
Etha.
Ext.
100 B C D*
180 Ocimum sanctum Leaf:
Aqua.
Ext.
100 A Kumar et al. 2014
100
(1-10d)
Panax ginseng
Root
100 Concomitant
(1-10d)
D E A Kalkan et al. 2012
200 AA A A
80
(1- 15d)
100 Concomitant
(1- 15d)
C B Qadir et al. 2011
80
(22-28d)
Red
ginseng
(root)
100 Preventive
(1-21) +
+ Concomitant
(22-28d)
A AA Lee et al. 2013
40
(1- 12d)
Physalis
alkekengi
Fruit:
Etha.
Ext.
450 Concomitant
(1- 12d)
B E
Ahmad et al. 2010
40
(1- 5d)
Curative
(6- 12d)
C E
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 11
80
(21 st d)
Phyllanthus
amarus
Leaf:
Etha.
Ext.
200 Preventive
(1- 20d)
A Sule and Arhoghro
2016b 300 B
40
(1- 14d)
Whole
plant:
Aqua
Ext.
100 Concomitant
(1- 14d)
E E
Adeneye and Benebo
2008
200 E D
400 D A
80
(4-11d)
Seed:
Meth.
Ext.
250 Preventive
(1- 3d) +
Concomitant
(4- 11d)
A A Bakhtiary et al. 2012
Seed:
Aqua.
Extract
300 E B
100
(1- 10d)
Phyllanthus
acidus
Leaf :
Meth.
Ext.
50 Concomitant
(1- 10d)
E A Vidya et al. 2013
100 E A
200 E A
80
(1-9d)
Phyllanthus niruri Whole
plant :
Meth.
Ext
200 Curative
(10-19d)
C A A Gaddam et al. 2015
400 B A A
80
(1-8d)
Phyllanthus
fraternus
Shoot :
Meth.
Ext.
100 Curative
(9-16d)
E D Kalyani et al. 2012
200 A A
80
(1-8d)
200 Concomitant
(1- 8d)
B B
100
(1- 8d)
Pimpinella
anisum
Shoot :
Eth. Ext.
300 Concomitant
(1- 8d)
E E Ashtiyani et al. 2017
80
(8-14d)
Piper cubeba Berry
(Dry)
Powder
810 Preventive
(1-7d)
+ Concomitant
(8-14d)
C E
Zaid et al. 2012
1220 C C
80
(1-7d)
810 Curative
(8-14d)
C C
1220 E C
40
(1-13d)
Pongamia pinnata Flower:
Eth. Ext.
600 Concomitant
(1-13d)
C A
Shirwaikar et al. 2003
Curative
(14-23d)
B A
100
(1-8d)
Punica granatum Fruit:
Aqua
ext.
100
Concomitant
(1-8d)
B D B*
Ali and Saeed 2012
Concomitant
(8th d)
E E A*
100
(4-8d)
Rheum emodi Revand
Hindi
(drug):
Metha.
Ext.
350 -
Water
solu.
Preventive
(1-3d) +
Concomitant
(4-8d)
D D
Alam et al. 2005
350 -
Water
insolu.
A D
Yadav et al.12
100
(1-8d)
Rubus ellipticus Fruit:
Pet.
Ether
Ext.
200
Concomitant
(1-8d)
C A E Sharma and Kumar
2011
Fruit:
Etha.
Ext.
A A A
Fruit:
Aqua
Ext.
A A C
100
(1-10d)
Rosmarinus
officinalis
Leaf :
Aqua
Ext.
220 Concomitant
(1-10d)
A AA C* Azab et al. 2014
80
(1-21d)
Rosa damascene
+ Cichorium
intybus
Flower
(Rosa) +
Root
(Cichori
um ):
Aqua
Ext.
250
(RD)
Concomitant
(1-21d)
E E E Khaliq et al. 2014
500
(RD)
E E E
250
(CI)
E E E
500
(CI)
E E E
250
(RD)
+250
(CI)
E E E
500
(RD) +
500
(CI)
C D E
80
(1-10d)
Sesbania
grandiflora
Leaf :
Aqua
Ext.
300 Concomitant
(1-10d)
A A A* Padmalochana and
Dhana rajan 2015
Leaf:
Etha.
Ext.
A A A*
Leaf :
Acetone
Ext.
A A A*
100
(1-10d)
Strychnos
potatorum
Seed:
Etha.
Ext.
100 Concomitant
(1-10d)
C E
Varghese et al. 2011
200 A B
300 A B
80
(1-21d)
Tamarindus
indica
Fruit:
Hydro-
Etha.
Ext.
200 Concomitant
(1-21d)
C A/A* Ullah et al. 2014b
80
(1-7d)
Tecoma stans
Flower:
Etha.
Ext.
500 Concomitant
(1-7d)
E C AA* Mohan et al. 2016
80
(1-8d)
Flower:
Ethyl
acetate
Ext.
100 Concomitant
(1-8d)
C E D/A* Raju et al. 2011
200 B E C/A*
300 A E A/A*
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 13
80
(1-7d)
Terminalia
chebula
Aqua
Ext.
125 Concomitant
(1-7d)
A A Sivachandran and
Hariharan 2012 250 A A
80
(1-7d)
Trema guineensis Leaf:
Hydro
hydro
Etha.
Ext.
100 Concomitant
(1-7d)
B C
Cyril et al. 2016
200 B C
Leaf :
Aqua
extract
100 A C
200 A C
100
(1-14d)
Trianthema
portulacastrum
Leaf :
Etha.
Ext.
200 Concomitant
(1-14d)
A AA B Balamurugan et al.
2009
80
(1-8d)
Tribulus terrestris
Fruit:
Aqua
ext.
(Kwath)
4000 Concomitant
(1-8d) +
Curative
(9-21d)
D E
Kulkarni et al. 2012
Curative
(9-21d)
A E
100
(61-68d)
Vitis vinifera Seed: n-
Hexane
& Meth.
Ext.
40 Preventive
(1-60d) +
Concomitant
(61-68d)
E E Safa et al. 2010
100
(15-22d)
Withania
somnifera
Root :
Meth.
Ext.
500 Preventive
(1-14d) +
Concomitant
(15-22d)
B B Choudhury et al.
2014
100
(1-8d)
Zea mays
Shoot:
Meth.
Ext.
200 Concomitant
(1-8d)
E C Sepehri et al. 2009
300 E D
400 E E
500 E E
Yadav et al.14
Table 3. Effects of herbal extracts on the recovery of biochemical markers of kidney health at different time intervals.
GM
(mg/
kg
B. wt)
Plant Herbal
Prep. Dose Protocol
mg/kg
B. wt
Day/
Week
Prognosis: Kidney
functions
References
U C BUN/UA
80
(6-10d) Aloe
barba-
densis
Leaf:
Ethan.
Extr.
20mL +
20mL =
40mL
Preventive
(1-5d) +
Concomitant
(6-10d)
10d
D D Virani et
al. 2016
80
(16-20d)
Preventive
(1-15d) +
Concomitant
(16-20d)
20d A B
80
(26-30d)
Preventive
(1-25d) +
Concomitant
(26-30d)
30d A A
80
(1-21d)
Citrus
aurantium
Fruit:
Etha.
Ext.
200 Concomitant
(1-21d)
1d AA AA/A* Ullah et al.
2014a 11d A AA
/A*
21d B AA
/A*
100
(11-18d)
Mangifera
indica
Fruit:
Vimang
(Comm-
ercial
Ext.)
50 Preventive
(1-10d) +
Concomitant
(11-18d)
11d C A
Rad et al.
2011
18d E D
100 11d C A
18d E D
Fruit:
Hydro-
alcoholic
Ext.
200 11d AA A
18d A AA
400 11d A C
18d C AA
100
(11-18d)
Fruit:
Vimang
100 Concomitant
(11-18d)
11d AA
A
18d E E
Fruit:
Hydro-
alcoholic
Ext.
400 11d AA A
18d D AA
80
(1-21d)
Mentha
piperita
Leaf :
Etha.
Ext.
200
Concomitant
(1-21d)
0d AA
AA
/A* Ullah et al.
2013c 11d AA
AA
/A*
21d B AA /A*
80
(1-10d)
Moringa
oleifera
Leaf :
Hydro-
Etha.
Ext.
150
Concomitant
(1-10d)
0d AA A
Ouédraogo
et al. 2013
4d A A
300 7d C B
10d E B
0d AA AA
4d A AA
7d B C
10d C A
80 Morus
alba
Fruit :
Etha.
Ext.
200 Concomitant
(1-21d)
0d
A A/A* Ullah et al.
2015 (1-21d) 11 d B A/A*
21 d D B/A*
100
(1-7d)
Myrme-
codia
tuberose
Tuber :
Aqua
Ext.
1000 Concomitant
(1-7d)
0 d
A A Sujono et
al. 2014 7 d E E
2000 0 d A A
7 d B C
4000 0 d B A
C 7 d B
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 15
80
(1-26d)
Nigella
sativa
Seed oil 2mL/kg Concomitant
(1-26d)
1d AA B Rehman et
al. 2012 10 d A A
14 d AA B
18 d AA AA
22 d AA A
26 d AA A
80
(1-10d)
Curative
(11-26d)
1d AA E
10 d E E
14 d E C
18 d D C
22 d C D
26 d C A
80
(1-26d)
Seed oil
2mL
/kg
Concomitant
(1-26d)
0d AA
C Saleem et
al. 2012 4d C A
8d AA A
12d AA AA
16d AA A
20d AA A
10 mM
(31-40d)
Panax
ginseng
Root:
Aqua
Ext.
100 Preventive
(1-30d)
+
Concomitant
(31-40d)
3d A A
Shin et al.
2014 10d E E
80
(1- 6d)
Phoenix
dactylifera
Fruit
flesh :
Aqua
Ext.
50% of
diet
Concomitant
(1- 6d)
6d A A Al-Qarawi
et al. 2008
Preventive
(1- 22d) +
Concomitant
(23- 28d)
28d A A
Pits:
Aqua
Ext.
Drin-
king
water
(2:1)
Concomitant
(1- 6d)
6d
A
A
Preventive
(1- 22d) +
Concomitant
(23- 28d)
28d A A
Yadav et al.16
Table 4. Ameliorative role of plant species on biochemical markers of kidney health and oxidative stress.
Dose
mg/kg
B. wt
Plant Herbal
Prep. Dose Protocol
mg/kg
B. wt
Prognosis References
Kidney functions Oxidative stress
U C BUN
/UA*
LPO/
MDA*
GSH/
GPX*
CAT SOD
100
(9-16d)
Aegle marmelos
Leaf:
Aqua Ext.
250 Preventive
(1-8d) +
Concomitant
(9-16d)
E E E E*
D D Kore et al. 2011a
500 D C D C*
C D
750 A A A A* B B
40
(1- 13d)
Alangium salvifolium
Bark:
Ethan. Ext.
250 Concomitant
(1-13d) + Curative
(14-21d)
E D B* D B Geetha and Ramarao
2014
500 B E A* D A
750 E A A* A A
750 E A C* D A
80
(1-14d)
Allium
sativum
Clove:
Aqua Homo.
500 Concomitant
(1-14d)
D* B*
Fadil et al.
2016
80
(NA)
Amorpho-
phallus
paeoniifolius
Corm:
Metha. Ext.
250 Not available E D C B Madhurima
2010 500 C A A A
100
(1- 7d)
Apium
graveolens
Var.rapaceum
Dry
powder of
Celery
5%
of
diet
Curative
(8-56d)
A A A* C * C C El-Ghany et
al. 2012
40
(1-14D)
Aristolochia indica
Leaf:
Ethan.Ext.
500 Concomitant
(1-14d)
AA
C A* C/A
* A A Arivazhagan
and Vimala-
stalin 2014
40
(1- 30d)
Asarum europaeum
Leaf:
Ethan. Ext.
200 Concomitant
(1- 30d)
C E E* D C Mamilla-pallai and
Akkiraju
2015
400 B E C* C B
80
(1-15d)
Bacopa
monniera
Shoot:
Ethan. Ext.
100 Concomitant
(1-15d)
A A C* B/A
* B B Kannan et al.
2011
200 AA A C* A/A* A A
80
(1-7d)
Barringtonia acutangula
Leaf :
Metha. Ext.
200
Concomitant (1-7d)
E E E B* B D Mishra et al.
2014
80
(1-8d)
Bauhinia
purpurea
Bark:
Eth. Ext.
400
Concomitant
(1-8d)
E E E* C
C Rana et al.
2014
Unripe Pod:
Eth. Ext.
E E E* C C
85
(21-28d)
Beta vulgaris
Root :
Eth. Ext.
250
Preventive
(1-20d) +
Concomitant
(21-28d)
E E E* E
*
A
EL Gamal et
al. 2014
500 E E E* E* A
80
(1-14d)
Calotropis procera
Flower:
Aqua Ext.
150 Concomitant
(1-14d)
B A A Javed et al. 2015
300 A A A
80
(1-6d)
Casuarina
equisetifolia
Leaf:
Metha.
Ext.
300 Curative
(7-35d)
C A AA* A* A
A El-Tantawy et
al. 2013
80
(29-34d)
300 Preventive
(1-28d)
A A AA*
A* A A
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 17
100
(50 + 50
twice )
(1-15d)
Camellia sinensis
Tablet of green tea
Ext.
300 Concomitant
(1-15d) +
Curative
(16-30d)
C C A A Salem et al. 2010
80
(1-7d)
Leaf:
Metha.
Ext.
300 Concomitant
(1-7d)
E B A A A Khan et al. 2009
80
(15-22d)
Citrus medica Fruit :
Etha. Ext.
250 Preventive
(1-14d) +
Concomitant
(15-22d)
E D E* E
* AL-Yahya et
al. 2015 500 E C E* E*
100
(1-24d)
Cocos
nucifera
Milk 1mL/
day
Concomitant
(1-24d)
A A A* A A Ehimigbai
and Ananobi
2015
80
(1-16d)
Inflo. sap powder
20 Concomitant
(1-16d)
A A A* B/A
* A A Jose et al.
2017
80
(10-19d)
Cucumis
sativus
Seed:
Hydro-
ethanolic Ext.
200 Preventive
(1-9d)
E D E D D C Pransanthi
and Adikay
2016 400 C B E C B B
80
(1-9d)
200 Curative
(10-19d)
D C E D C C
400 A A D A A B
100
(8-15d)
Curcuma longa (CL)
Rhizome: Curcu-
min
200 Preventive
(1-7d) +
Concomitant
(8-15d) +
Curative
(16-57d)
B A A/A* A A El-Zawahry
and Kheir
2007
80
(5-10d)
200 Preventive
(1-4d) +
Concomitant
(5-10d)
C B A A Ali et al. 2005
100
(8-15d)
100 Preventive
(1-7d) +
Concomitant
(8-15d)
A B
A* A Bayomy et al.
2011
100
(15-21d)
200 Preventive
(1-14d) +
Concomitant
(15-21d)
B B E* A/A
* A A Farombi and
Ekor 2006
100
(1-7d)
CL Powder with diet
5% Curative
(8-56d)
A B E* B* C B El-Ghany et al. 2012
80
(36-42d)
CL Rhizome
powder:
Aqua Ext.
150 Preventive
(1-35d) +
Concomitant
(36-42d)
B A A* A
A* B/C
* B A Shalaby &
Hammouda
2014
Eruca sativa
(ES)
Seed:
Aqua Ext.
150 B A A* A
* A/B
* A A
Petroselinum Seed: 150 B A A* AA* C/C* C B
Yadav et al.18
CL + PS + ES
As above 50+50+50
A AA A
* A
* A/A
* A A
100
(6-12d)
Crocus
sativus
Pigment
crocin:
Aqua extract
100 Preventive
(1-5d) +
Concomitant
(6-12d)
E E A*
Yarijani et al.
2016
80
(6-10d)
Saffron:
Aqua Ext.
40 Preventive
(1-5d) +
Concomitant (6-10d)
D E E* Ajami et al.
2010
80 C C C
*
100
(1-10d)
Cynara
scolymus
Leaf:
Aqua Ext.
200 Concomitant
(1-10d)
B C/B* B Khattab et al.
2016 400 A A/A* A*
600 A AA/A* A*
100
(4-10d)
Cyperus scariosus
Root :
Hydro alcoholic
Ext.
150 Preventive
(1-3d) +
Concomitant
(4-10d)
E E
E* A
E Gajjar et al. 2016
100
(1-7d)
Curative
(8-18d)
A A E* E D
100
(4-10d)
250 Preventive
(1-3d) +
Concomitant (4-10d)
E E C* C D
100(1-7d) Curative (8-18d) A B A* E D
100
(3-10d)
Euclea
divinorum
Leaf:
Crude Ext.
100 Preventive
(1-2d) +
Concomitant (3-10d)
D A A* A A A Feyissa et al.
2013 150 E C A* A A A
200 E D A* A C A
Metha. fraction
100 B A A* A A A
Aqua
fraction
100 AA A A
* E B A
100
(1-6d)
Elaeocarpus ganitrus
Seed:
Etha. Ext.
100 Concomitant (1-6d)
E E/A*
C A A Kakalij et al. 2014 200 E D/A
* B A B
400 D A/
AA*
A A C
80
(1-8d)
Enicostemma
littorale
Whole
plant
Metha. Ext.
2500 Concomitant
(1-8d)
E D D* E/C* A A Bhatt et al.
2011
120
(1-7d)
Ferulago
angulata
Whole
plant :
Hydro-
Etha. Ext.
200 Concomitant
(1-7d)
E E E* E
* C C Valipour et al.
2016 400 E AA D
* E
* C E
800 C E B* A
* A B
80
(1-21d)
Foeniculum vulgare (FV)
&
Solanum
nigrum (SN)
Seeds of FV
and Fruits
of SN
250 (FV) Concomitant
(1-21d)
A A
E* B
Shaheen et al. 2014 250
(SN) A A E
* B
500
(FV)
AA A C* A
500(SN) AA A D
* A
250
(FV) +
250 SN)
A A D* B
500 (FV) + 500
(SN)
AA A
A A
* A
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 19
200
(1-8d)
Ficus carica Fruit:
Hydro-
Etha. Ext.
250 Concomitant
(1-8d)
E E E E* D D Kore et al.
2011b 500 D C D C
* C D
750 A A A A* B B
80
(1-11d)
Ficus racemosa
Bark:
Aqua Ext.
200 Concomitant
(1-11d)
A A A A C C Shivalinge and
Vrushaben-
dra 2012
400 A A A A C C
80
(1-12d)
Glycine max Seed:
Phenolic
ext.
500 Concomitant
(1-12d)
A A A
B Ekor et al.
2006 1000 A A E A
100
(8-12d)
Glycyrrhiza glabra
Capsule 150 Preventive
(1-7d)
A A/A* A* C Yousef and Alkreathy
2016
40
(1-13d)
Grapto-
phyllum pictum
Leaf:
Phenolic Ext.
75 Curative
(14-23d)
A E
A A E Srinivasan et
al. 2015 150 A E A A A
300 A E A A A
100
(1-12d)
Houttuynia
cordata
Leaf :
Metha.
Ext.
500 Concomitant
(1-12d)
B E A* A A B Kang et al.
2013
1000 A B AA* A
A A A
80
(1- 5d)
Ipomoea
digitata
Root :
Ethan.
Ext.
500 Concomitant
(1- 5d)
A AA B
* A Kalaiselvan et
al. 2010
80
(1-10d)
Lavandula
officinalis
Leaf:
Etha. Ext.
100 Concomitant
(1-10d) +
Curative
(11d)
E E E* C Kalantar et al.
2016 200 E E AA * B
400 E B C* A
100
(1-8d)
Macrothe-lypteris
oligophlebia
Rhizome :
Etha. Ext.
250 Concomitant
(1-8d)
C C A* D
* A A Wu et al.
2012
500 A B A* A
* A A
40
(1-13d)
Mimosa pudica
Root:
Etha. Ext.
200 Concomitant
(1-13d) + Curative
(14-21d)
E E C* A B Geetha et al.
2015 400 E D A* B A
600 E B A* C A
600 Curative
(14-21d)
E D C* A A
100
(1-6d)
Mucuna pruriens
Seed:
Aqua Ext.
200 Concomitant
(1-6d)
B C E C B B Modi et al. 2008 400 A A E A A A
80
(35-42d)
Momordica dioica
Leaf :
Etha. Ext.
200 Preventive
(1-34d) +
Concomitant
(35-42d)
E E C C/A* E C Manimala et
al. 2015 400 D E A C/A* B A
40 Fruit 200 C E A* C Jain and
Singhai 2010 200 C E D
* A
50 +50
(8-12d)
Moringa
oleifera
Leaf:
Powder
10,000 Preventive
(1-7d) +
Concomitant
(8-12d)
B A A* B/A
* A A Elazab and
El-Habashi
2015
Yadav et al.20
100
(1-14d)
Nelumbo nucifera
Flower:
Etha. Ext.
200 Concomitant
(1-14d)
A E
C* A/B
* A A Saraswathi
and Shoba
2015
400 AA C B
* A/A
* A A
80
(1-6d)
Nigella sativa Seed Oil 0.2mL/kg
Concomitant
(1-6d)
B C A* A* A Yaman and Balikci 2010
0.4
mL/kg
A A A* A* A
100
(1-8d)
Seed :
Hexane
Ext.
5 mL
/kg
Concomitant
(9-15d)
E B Begum et al.
2006
100
(1-7d)
Ocimum
gratissimum
Leaf :
Aqua.
Ext.
100 Curative
(8-14d)
A E
A Ogundipe et
al. 2016 200 A D A
400 A D A
70
(1-28d)
Olea europaea
Leaf :
Etha. Ext.
20 Concomitant
(1-28d)
E E
C* B* D A Abd El-Rahman 2016 40 D D B
* A
* C A
80 E C A* B
* C A
160 B* B
* C A
80
(1-7d)
Oroxylum
indicum
Whole
plant :
Metha. + Dichloro
methane
Ext.
200 Concomitant
(1-7d)
E E E* B
* B A Mishra et al.
2014
80
(1-9d)
Orthosiphon
stamineus
Metha.
Ext.
100 Curative
(10-19d)
C E C Kannappan et
al. 2010
200 A A A
200 Preventive A A A
100
(1-10)
Panax
ginseng
Root 200 Concomitant
(1- 10d)
C C A* C/A
* B Karadeniz et
al. 2008b
100
(1- 8d)
Pedalium
murex
Fruit :
Eth. Ext.
600 Concomitant
(1- 8d)
D B B A A
Sreedevi et al.
2011
Fruit :
Aqua. Ext.
A A A A A
100
(1-14d)
Pistacia
khinjuk
Fruit :
Eth. Ext
150 Concomitant
(1-14d)
E E B* A
Ghaedi et al.
2014 300 E D A* A
600 A A A* A
80
(1-15d)
Portulaca
oleracea
Whole
plant: Aqua.
Ext.
400 Concomitant
(1-15d) A A A
* B
* A A A Mouhamed
and Elshafeey 2011
80
(4-11d)
Psidium
guajava
Leaf:
Etha.
Ext.
200 Preventive
(1-3d) +
Concomitant (4-11d)
C E
A A
Patel et al. 2012
400 A
A A
A A
A A
80
(1-8d)
Punica
granatum
Fruit :
Ext.
150 Concomitant
(1-8d)
AA *
Primarizky et
al. 2016
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 21
100
(1-6d)
Fruit :
Aqua Ext.
100µL Concomitant (1-6d)
C E A* A Cekmen et al.
2013
100
(3-9d)
Flower:
Hydro
Ethan. Ext.
25 Preventive
(1-2d) + Conc-
omitant (3-9d)
A A D*
Sadeghi et al.
2015 50 D E
E*
80
(5-10d)
Rhazya stricta Leaf:
Aqua ext.
250 Preventive
(1-4d) +
Concomitant
(5-10d)
E E
C
C Ali 2002
500 E E A A
1000 D A A A
100
(1-15d)
Rheum emodi Rhizome: Chloro.
Ext.
100 Concomitant (1-15d)
E E
Aslam et al. 2014
Pet Ether Ext.
100 E E
Chloro.
Ext. fractions
50
SBF *
SCF*
SH*
CHL* RE*
E E E A A A
D E E A A C
E D E A E A
C E E A A B
E E E D C E
100
(1-8d)
Sida rhom-boidea
Leaf: Aqua Ext.
200 Concomitant
(1-8d)
C C N
A
E B D E Thounaojam et al. 2010
400 B A C A B C
100
(1-8d)
Sida
cordifolia
Root:
Aqua Ext.
200 Concomitant
(1-8d)
E E E
A B Makwana et
al. 2012 400 E E C A A
100
(1-5d)
Sesamum
indicum
Seed
oil
0.5mL
/kg
Concomitant
(1-5d)
A A A Hsu et al.
2011
80
(4-11d)
Spathodea
campanulate
Bark:
Eth. Ext.
250 Preventive
(1-3d) Conc-omitant (4-11d)
AA B
AA C
Shanmukha et
al. 2010 500 AA A
A A
A B
100
(1-8d)
Solanum
nigrum
Aqua
Ext.
100 Concomitant
(1-8d)
B C A A A Priya and
Venkata-
lakshmi 2011
100
(1-8d)
Solanum
xantho-
carpum
Fruit:
Eth. Ext.
200 Concomitant
(1-8d)
A A A A C C C Hussain et al.
2012
400 D C B C AA E AA
100
(1-10d)
Sonchus asper
Whole plant:
Meth. Ext.
100 Concomitant
(1-10d)
B E
A C C Khan et al. 2011
200 B C A B A
40
(1-7d)
Tephrosia
purpurea
Leaf :
Eth. Ext.
200 Curative
(7-16d)
Concomitant
(1-7d)
B E
E* A
C Jain et al.
2013
C
E
C*
C
A
80
(1-14d)
Terminalia
ivorensis
Stem bark
:Eth. Ext.
100 Concomitant
(1-14d)
C E B C B B Ansah et al.
2016
800 A C A B A A
1000 A D A A A A
80
(1-15d)
Terminalia
bellerica
Stem:
Etha. Ext.
500 Concomitant
(1-15d)
D A C* C* B B B Fatima and
Sultana 2016
Aqua Ext.
B A A* A
* A A A
80
(1-8d)
Sphaeranthus
indicus
Whole
plant: Eth. Ext.
150
300
Curative
(9-19d)
E E A/A* A A Mathew et al.
2009
A E A/A* A AA
Yadav et al.22
Fractions of chloroform Ext.: SBF = NaHCO3 fraction, SCF = Na2CO3 fraction, SHF = Sodium hydrate fraction, CHL=
solutes in left out chloroform layer, RE = ppt formed after adding NaHCO3 in chloroform Ext.
Table 5. Ameliorative role of plant species on biochemical markers of kidney health and oxidative stress at different time
intervals.
80
(1-14d)
Trachy-sp erm um am mi
Seed:
Aq ua Ext.
3 00 Co nco mitan t
(1 -14d)
A A A
A
Ishaq et al. 201 5 6 00 A A A AA A
400 Trian thema po rtula-castrum
Whole plant
po wd er
1 00 0 NA B A A* C C /A * C V allabi and E lango 2015
100
(1-8d)
Trichosa n-th es dioica
Leaf:
Meth . Ext.
2 00 Co nco mitan t
(1 -8d)
E E C E C C C G upta et al . 201 5 4 00 C C B AA A B B
100
(1-8d)
Trigo nella
fo enu m graceum
Seed:
Aq ua Ext.
2 00 Co nco mitan t
(1 -8d)
E E E* D D
K aur et al .
201 6 4 00 D E E* C D
8 00 B E D* A A
100
(1-10d)
Urtica dio ica Leaf:
Eth. Ext.
1 00 Co nco mitan t
(1 -10 d)
A A A* E Sal ih 2015
80
(1-7d)
Vitex
negun do
Root :
Meth a. + Dichloro methane
Ex t.
2 00 Co nco mitan t
(1 -7d)
D D
C* B * B A Mishra et al.
201 4
80
(8-21d)
Vitis vin ifera Seed Ext . 1 50
Preventive
(1-7d) +
Co nco mitan t
(8 -21d)
A C C* B
/A*
El- Ashmawy et al. 2 006
100
(1-7d)
Zingiber
of ficinale
Rhizome
Pow der
5 % of
d iet
Cu rat ive
(8-56d)
A A A* D * C B El-G hany et
al . 201 2
100
(1-7d)
Rhizome: gingerol
fraction
6 .25 Co nco mitan t
(5-7d)
Cu rat ive
(8-9d)
C C E E* D C Ro drigues et al . 201 4 1 2.5 A B E D* C C
2 5 A A A B A* A B
GM
(m g/Kg
B . wt)
P lant
Herbal
Prep- Dose P rotocol
ration m g/kg
B. wt
Da y P rognosis References
Kidne y functions Oxid a tive stres s
U C B UN/
UA *
LPO /
M DA*
GSH/
GPX*
C AT SOD
150
(1-10d)
B oerhavia
diffusa
Aque ous
E xt. of
whole
plant
200 Conc om ita nt
(1-10 d)
1d
A A A
B*
A
Sa wardekar
and Pa te l
2015 11d A A
400 1d AA
A
A *
A 11d D B
80
(1-8d)
Hy gro-
phila
spinosa
E than.
E xt. of
whole
plant
50
Curative
(9-30 d)
1d AA
AA
Bibu e t al.
2010 9d E E
15d D E
30d A A E C E E E
250 1d AA
AA
9d E E
15d A A A
30d AA
AA
AA
E E E
Dungca
2016 80
(1-8d)
E clipta
alba
L eaf:
M eth.
E xt.
300
600
Conc om ita nt
(1-8d )
0d AA
AA
8d A A C A A
0d A A A
8d AA
C AA
C
80
(1-9d)
V erbas-
c um
thapsus
L eaf:
M eth.
E xt.
250 Conc om ita nt
(1-9d )
1d A A A
Pa l et al.
2013 3 d C A C
5 d AA
A C
9 d D A D D E C C
500 1 d A A A
3 d B A B
5 d B A B
9 d C A A E C B A
PROTECTIVE ROLE OF PLANTS AGAINST GENTAMICIN INDUCED NEPHROTOXICITY 23
Seed: Glycine max, Kalonchoe, Phyllanthus amarus,
Sesamum, Mucuna, Cucumis sativus
Fruit: Rubus elliptus, Phoenix dactylifera, Pedalium,
Pistacia, Solanum xanthocarpum
Milk: Cocos nucifera
Whole plant: Boerhavia, Orthosiphon, Portulaca
Curcuma rhizome in combination with seeds of
Petroselinium and Eruca improved kidney function to good
category.
· Moderate protection/recovery in kidney functions
was observed when plant parts of following plant
species were administered to the gentamicin treated
animals (Table 2-5).
Belowground organs
Root: Andrographis, Daucus
Rhizome: Curcuma longa, Macrothelypteris, Nelumbo
Aboveground organs
Leaf: Aristolochia, Bauhinia variegata, Dalbergia,
Eclipta, Houttuynia, Rosamarinus, Sida rhomboidea,
Trema, Verbascum and Trianthema
Shoot: Bacopa, Terminalia bellerica, Terminalia
ivorensis
Seed: Elettaria, Eruca, Lagenaria, Petroselium,
Strychnos, Vitis vinifera
Flower: Nelumbo nucifera, Pongamia pinnata
Fruit: Bauhinia purpurea, Tamarindus indica, Morus alba
Whole plant: Trianthema, Phyllanthus niruri
· The plant parts of following species belonged to
excellent category for protection/recovery of
oxidative stress and antioxidant levels (Table 4,5).
Leaf: Houttuynia, Psidium
Whole plant: Sphaeranthus
Fruit: Punica
· The plant parts of following plant species belonged
to good category for protection/recovery of
oxidative stress and antioxidant levels (Table 4, 5).
Belowground organs
Root: Sida cordifolia
Rhizome: Curcuma longa, Macrothelypteris
Corm: Amorphillus
Aboveground organs
Leaf: Casuarina, Camellia sinensis, Cynara, Euclea,
Graptophyllum, Ocimum gratissimum, Rhazya
Shoot: Bacopa, Terminalia bellerica
Bark: Alangium, Terminalia ivorensis
Flower: Calotropis, Cocos nucifera
Fruit: Pedalium, Pistacia
Milk: Cocos nucifera
Seed: Punica, Sesamum, Nigella, Trachyspermum
Whole plant: Boerhavia, Orthosiphon
Combination: Curcuma (rhizome) + Petroselinium (seed)
+ Eruca (seed)
Foeniculum (seed) + Solanum nigrum (fruit)
The plant parts of following plant species belonged
to moderate category for protection/recovery of
oxidative stress and antioxidant levels (Table 4, 5).
Belowground organs
Root: Vitex, Glycyrrhiza, Ipomea digitata, Mimosa
pudica, Panax
Aboveground organs
Leaf: Aegle, Aristolochia, Eclipta, Lavandula,
Momordica dioica, Moringa, Olea, Sida rhomboidea,
Tephrosia, Trichosanthes
Bark: Ficus racemosa, Spathodea
Flower: Cocos, Momordica dioica, Nelumbo
Seed: Eruca, Elaeocarpus, Foeniculum, Petroselinum,
Glycine, Vitis
Whole plant: Portulaca, Ferulago, Sonchus, Trianthema
Punarnava (Boerhaavia diffusa), Gokshur (Tribulus
terrestris), Haritaki (Terminalia chebula), Neem
(Azadirachta indica), Daruharidra (Berberis aristata) and
Patol (Tricosanthes dioica) are some of the species used in
treating kidney disorders in the Ayurvedic treatment. Bilvadi
agada is an ayurvedic drug having nephroprotective role in
gentamicin exposed Wistar rats (Kanna et al.2015). It is
mixture of Aegle marmelos, Ocimum sanctum, Pongamia
pinnata, Valeriana wallichi, Cedrus deodara, Phyllanthus
emblica, Terminalia chebula and Terminalia bellirica,
Zinziber officinale, Piper nigrum, Piper longum, Curcuma
longa, Berberis aristata and goat's urine.
Interestingly, Aegle marmelos (Moderate), Boerhaavia
diffusa (Excellent), Curcuma longa (Moderate),
Ocimum sanctum (Good), Pongamia pinnata
(Moderate), Tribulus terrestris (Moderate), Terminalia
chebula (Excellent), Terminalia bellirica (Moderate),
Yadav et al.24
Tricosanthes dioica (Moderate) and Zinziber
officinale (Moderate) were also found renoprotective in
the experimental studies (Table 2,4).
Out of 142 species (angiosperms) screened in the gentamicin
treated animals, majority (105 species) were effective
(moderate – excellent) for renoprotection and reducing
oxidative stress. Many of them are used in preparing
renoprotective drugs in the Ayurvedic system. Plant species
of excellent category may be explored for ameliorative role
to other nephrotoxicants singly as well as in various
combinations. The recommended dose of gentamicin for
human is 20µg/kg body weight while several plant species
were excellent in term of protection to experimental animals
even at its higher doses (80-100mg/kg body weight), and
therefore, there is a good scope for their clinical trials in the
human beings treated with gentamicin.
Presence of renoprotective properties among such a vast
number of species highlights role of biodiversity in the welfare
of mankind. Cuscuta considered as an obnoxious stem
parasite is a very interesting example that nature blesses to
the mankind because of its excellent renoprotective
properties. Several of renoprotective species are cultivated
for human consumption while others grow wild on
wastelands, farmlands and forests. Interestingly many of them
are used daily in the preparation of the Indian cuisines.
Interestingly few of the most promising renoprotective plant
species grow luxuriantly on wastelands, farmlands and forests
in the Rajasthan. Thirty two plant species growing wild or
naturalised in the State of Rajasthan have been screened for
their reno-protective role. These are; Abutilon indicum,
Acacia senegal, Adhatoda zeylanica, Aegle marmelos,
Aloe barbadensis, Bacopa monniera, Bauhinia purpurea
,Bauhinia variegate, Boerhavia diffusa, Boswellia
serrata, Calotropis procera, Citrullus colocynthis,
Cuscuta reflexa, Dalbergia sissoo, Eclipta alba,
Gomphrena celosioides, Ipomoea aquatica, Nelumbo
nucifera, Pedalium murex, Phyllanthus niruri, Portulaca
oleracea, Sida cordifolia, Solanum nigrum, Solanum
xanthocarpum, Sonchus asper, Tamarindus indica,
Terminalia bellerica, Terminalia chebula, Trianthema
portulacastrum, Tribulus terrestris, Vitex negundo and
Withania somnifera. Out of these 32 species, 3 species
were excellent (Acacia senegal, Cuscuta reflexa, Eclipta
alba) while others were good to moderate for
renoprotection. Natural calamities such as drought, diseases
(microbial and viral) and insect damages affect their growth
little since these have evolved through natural selection. Their
cultivation may be promoted on wastelands and farmlands
in the rural areas to prosper sustainable development since
these are less demanding in comparison to conventional
crops.Various government organizations should come forward
in developing technology for cultivation of elite renoprotective
species, network for their collection and storage practice
after harvest and linkage with Pharma industry. Such
interventions will benefit farmers particularly those enganged
in subsistence farming while country will be benifitted by their
export because of increasing demand for herbal drugs
globally.
ACKNOWLEDGEMENTS
Thanks are due to the CSIR, New Delhi for awarding SRF
to Dr. Nirmala Yadav, UGC, New Delhi for UGC Post
Doctoral Fellowship to Dr. Shweta Sharma and UGC
Emeritus fellowships to Professor Subhasini Sharma and
Professor K. P. Sharma and Heads, Department of Botany
& Zoology, Univ. of Rajasthan, Jaipur for laboratory facilities.
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